The objectives of the research proposed here are to analyze cytotoxic T lymphocyte lines (CTLLs) generated in vitro against murine plasmacytoma associated antigens, and to define the detailed target cell specificities against which these lines are directed. In order to accomplish these aims, CTLLs will be generated from normal lymphoid cells by multiple stimulations with plasma cell tumors, will be propagated in T cell growth factor, and will be cloned to produce lines which are reactive with individual antigenic determinants. The first major emphasis of these investigations will be to use these cloned lines to study the complex array of tumor associated antigens which have been described on plasma cell tumors, particularly whether the major histocompatibility gene products play a role in the cytotoxic T cell response to these antigens. A second major emphasis will be to characterize the CTL populations and cloned lines for cell surface phenotype and in vivo and in vitro activity. Cell surface analysis will be carried out by immunofluorescence using flow cytometry analysis, and will employ a battery of monoclonal antibodies against lymphoid differentiation antigens including Thy-1, Lyt-1 and Lyt-2. In vivo studies will include analysis of the activity of lines with different cell surface phenotypes, and with different specificities. The activity of various lines will be evaluated in both Winn type and immunotherapy models and when necessary, populations of cells with a select phenotype will be obtained by fluorescence activated cell sorting techniques. Effort will concentrate on correlating cell surface phenotypes with functional activity. The results of these investigations should 1) provide a better understanding of the characteristics of effector cells directed toward tumor associated antigens (TAAs); 2) provide information about the TAAs of PCTs recognized by cytoxic T cell responses; and 3) guide studies of human tumor immunotherapy with respect to protocols which may result in the generation of tumor-directed immunologically reactive cells which can be used for adoptive immunotherapy in the treatment of cancer patients.